A NATURAL ALTERNATIVE TO STATINS: HYPOLIPIDEMIC EFFECT OF TURNIPS IN AN EXPERIMENTAL MODEL OF HYPERLIPIDEMIA IN RATS
Abstract
The present study investigated the effect of Brassica rapa polysaccharides on body weight, blood chemistry, and digestive enzyme activity in rats with hyperlipidemia caused by a high-fat diet. Plant polysaccharides are able to regulate metabolism, have hypolipidemic and anti-inflammatory effects. In this study, the effect of Brassica rapa polysaccharides on body weight, glucose levels, and basic biochemical parameters of the blood lipid spectrum in laboratory animals was studied.
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SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 56 A NATURAL ALTERNATIVE TO STATINS: HYPOLIPIDEMIC EFFECT OF TURNIPS IN AN EXPERIMENTAL MODEL OF HYPERLIPIDEMIA IN RATS D.G. Abdugafurova1, D.A. Amanlikova2, M.Dj. Oripova3, Z.N. Qöziyeva3 Institute of Bioorganic Chemistry named A.S. Sadykov of the Science Academy of Uzbekistan1,2,3 https://doi.org/10.5281/zenodo.17445425 Abstraсt. The present study investigated the effect of Brassica rapa polysaccharides on body weight, blood chemistry, and digestive enzyme activity in rats with hyperlipidemia caused by a high-fat diet. Plant polysaccharides are able to regulate metabolism, have hypolipidemic and anti-inflammatory effects. In this study, the effect of Brassica rapa polysaccharides on body weight, glucose levels, and basic biochemical parameters of the blood lipid spectrum in laboratory animals was studied. Keywords: hyperlipidemia, metabolic diseases, cardiovascular diseases, turnip, Brassica rapa polysaccharides, hypolipidemic effect, experimental model, rats. Introduction. Hyperlipidemia is one of the key risk factors for developing metabolic and cardiovascular diseases. Lipid metabolism disorders are often accompanied by liver damage, pancreatic dysfunction, and changes in the activity of digestive enzymes. Induced hyperlipidemia is an experimental model widely used to evaluate the effectiveness of lipid-lowering drugs. The present study investigated the effect of Brassica rapa polysaccharides on body weight, blood chemistry, and digestive enzyme activity in rats with hyperlipidemia caused by a high-fat diet. Plant polysaccharides are able to regulate metabolism, have hypolipidemic and anti-inflammatory effects. In this study, the effect of Brassica rapa polysaccharides on body weight, glucose levels, and basic biochemical parameters of the blood lipid spectrum in laboratory animals was studied. The results showed that the use of polysaccharides was accompanied by a decrease in glucose and triglycerides, normalization of body weight and partial restoration of the lipid profile, which may indicate their potential ability to modulate lipid metabolism. The data obtained can serve as a basis for further research in the field of the development of phytotherapeutic agents of complex action in metabolic syndrome. The aim of this study was to evaluate the effect of polysaccharides isolated from Brassica rapa seeds on body weight dynamics, blood biochemical parameters and digestive enzyme activity in rats with induced hyperlipidemia. As part of the experiment, the dynamics of body weight, glucose, total cholesterol, triglycerides, high and low density lipoproteins in animal blood serum were studied. Analysis of the data obtained allowed us to establish that the introduction of Brassica rapa polysaccharides leads to normalization of biochemical parameters, which may indicate the presence of lipid-lowering activity in the compound. Material and methods. The use of polysaccharides isolated from Brassica rapa seeds in rats with hyperlipidemia. Hyperlipidemia was caused by the introduction of a high-fat diet (HFD) for 8 weeks. The diet consisted of 60% fat, 20% carbohydrates and 20% protein. Biochemical parameters (blood glucose, total cholesterol, TG, LDL cholesterol, HDL cholesterol), liver enzymes (AST, ALT) and enzymes of lipid metabolism. The animals were randomly divided into
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 57 4 groups of 10 rats each: 1. Control group (C): standard diet. 2. The hyperlipidemia (HFD) model: a high-fat diet. 3. Positive control (HFD+ Metmorphine): a high-fat diet + metmorphine (95 mg/kg body weight dose). 4. Group with polysaccharides (HFD + PS): high-fat diet + Brassica rapa polysaccharides (dose 20 mg/kg body weight). Polysaccharides and metmorphine were administered daily for 4 weeks. The Brassica rapa polysaccharide extract was obtained by hot water extraction followed by ethanol purification. Biochemical parameters were determined using standard kits: total protein by biuretic reaction, ALT and AST colorimetrically, amylase and glucosidase enzymatically. Polysaccharides extracted from rapeseed seeds have demonstrated potential in regulating lipid metabolism in animal models of hyperlipidemia. Assessment of body weight and digestive enzymes. The animals' body weight was measured weekly. The activity of digestive enzymes (amylases) was determined in blood serum using appropriate commercial kits. Biochemical analyses. After completion of the experiment, blood was taken from the tail vein to determine the following parameters: glucose, total cholesterol (OH), triglycerides (TG), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), aminotransferase activity (ALT, AST). Statistical processing of results Statistical processing of the obtained data was carried out using the Microsoft Office Excel computer program and the online MedStatictica program. Animal Ethics. All preoperative and experimental protocols have been thoroughly reviewed and approved by the Institutional Committee for the Use and Care of Animals. The animals were kept in the rooms of the vivarium under controlled conditions, with a relative humidity of 55-65%, an ambient temperature of 22 ± 2 ° C and had free access to water and regular laboratory feed. All procedures for the treatment and care of animals strictly comply with the European Directive 2010/63/EU on the protection of animals used for scientific purposes. The ethical approval of this study was received by the Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan, the Committee on Animal Ethics (Protocol No. 133/1a/h dated August 4, 2014). Results. The biological activity of polysaccharides depends on the molecular weight (MW), the composition of monosaccharides, the type of glycoside bonds, and the sulfate content [1]. In our studies, Brassica rapa polysaccharides belonging to the arabinogalactane type were used in doses of 25 mg/kg. Brassica rapa polysaccharides effectively reduce improve lipid profile due to their antioxidant and anti-inflammatory properties. Randomized clinical trials, clarification of bioavailability, pharmacokinetics, and long-term safety are necessary for implementation in clinical practice. Macroscopic examination of the organs of rats with hyperlipidemia showed that a high-fat diet in animals caused liver steatosis, inflammation, and amyloid deposition. Treatment with Brassica rapa polysaccharides at a dose of 25 mg/kg changed metabolism, reducing lipid levels using LPL, GPR reptors, and other targets. This is manifested in a decrease in total cholesterol (OH), triglycerides (TG), LDL cholesterol and fatty liver infiltration [2, 3], an increase in the expression of LPL (lipoprotein lipase) in the liver and adipose tissue, a key enzyme that promotes the utilization of triglycerides, as well as in the modulation of PPG receptors (in particular, GPR41/GPR43), involved in fatty acid metabolism and regulation by short-chain fatty acids (SCFA), in parallel, there is an improvement in the intestinal microbiota and SCFA production, which also activates PPG receptors, It helps to reduce lipid levels and inflammation [4]. A decrease in the concentration of markers (IL 6, TNF α, ICAM 1, VCAM 1), an increase in fat and energy balance [5, 6]. The authors pointed out that republic supports many active formats: presidents, isocyanates [7], turnip extract prevents obesity and suppresses the accumulation of fat cells; it induces the expression of β3-
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 58 adrenergic receptors (β3-AR) [8]. A study of the metabolic syndrome called lactose (multiple sclerosis) has shown that you are part of the leading group in the republic, which is an important indicator of an increase in blood lipids and increased levels of glutathione and liver glycogen in the blood, which indicates the positive influence of the republic on the mathematical world [9]. Hyperlipidemia, a pathological increase in blood lipids, has long been recognized as a risk factor for cardiovascular diseases. Brassica rapa seed leaves contain polysaccharides, trace elements and phytochemical compounds that have hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory effects. Induced hyperlipidemia is an experimental model widely used to evaluate the effectiveness of lipid-lowering drugs. The present study investigated the effect of polysaccharides on body weight, blood chemistry, and digestive enzyme activity in rats with hyperlipidemia caused by a high-fat diet. Plant polysaccharides, in particular polysaccharides isolated from brassica rapeseed, are able to regulate metabolism, have hypolipidemic and anti-inflammatory effects. Thus, brass polysaccharides effectively reduce the level of hyperlipidemia among the creators of Chris's film for annual joint events on the development of LPL, GPR41/GPR43, SCFA and space helmets. The mechanism by which lipid reduction is achieved is complex because it affects multiple targets and cellular signaling pathways [10]. Brassica rapa turnip seeds reduced glycemia, cholesterol, and LDL cholesterol, but a number of models showed elevated cholesterol, AST, and reduced HDL cholesterol. When eating high-fat foods in mice, TG and cholesterol accumulate in the liver, and the balance of HDL is disrupted/LDL, steatosis and inflammation develop. This study made it possible to plan and conduct studies on the effect of polysaccharides isolated from Brassica rapa seeds in glucose and lipid metabolism, which examines enzymes that regulate liver lipid activity, body weight dynamics with blood biochemical parameters and digestive enzyme activity, as well as the relationship between diabetes mellitus and hyperlipidemia in induced hyperlipidemia in rats. Consumption of Brassica rapa polysaccharide by animals was accompanied by a moderate increase in body weight in rats compared with the control group at a dose of 25 mg/kg. There was a statistically significant increase in the mass of the liver and spleen, which indicates the activation of metabolic and immune processes. The increase in body weight was not accompanied by a violation of the proportions of organ mass, which indicates the potential safety of the administered substance at this dose. When consuming a high-fat diet, mice accumulate TG and cholesterol in the liver, and the balance of HDL is disrupted/LDL, steatosis and inflammation develop. Animal studies with a hyperlipidemia model have shown: after 14 days, the levels of total protein, cholesterol, glucose, HDL and LDL in the blood serum approached the norm – 2.53–3.14 mmol/l (control – 8.40 mmol/l). Table 1 Initial and final parameters of animals during induction of hyperlipidemia for 75 days Parametrs Data Days of research The initial 20th day 40th day 60th day 75th day Dynamics of mass (gr.) 213,0 ±21,2 230,8 ± 22,8 277,5 ±26,7 315,0 ±30,2* 411,5 ±38,9*
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 59 Abdominal volume (cm) 15,5 ± 1,5 17,1 ± 1,6 18,4 ± 1,72* 21,8 ± 2,2* 23,0 ± 2,32* *- p<0.05 in relation to the control group Table 2 Changes in metabolic syndrome parameters in animals treated with hyperlipidemia for 14 days with metmorphine and Brassica rapa polysaccharides Parametrs Data The initial Control Metmоrfin 95 mg/kg BSP 25 mg/kg Dynamics of mass (gr.) 213,0 ± 21,2 411,5 ± 38,9 357 ± 34,9 334,3 ± 33,3* Abdominal volume (cm) 15,5 ± 1,5 23,0 ± 2,32 20,5 ± 2,0** 18,8 ± 1,8** Liver (mg) 7,8 ± 0,79 13,7 ± 1,4 12,6 ± 1,2** 9,4 ± 0,94** Heart (mg) 0,9 ±0,085 1,5 ± 0,13 1,5 ± 0,11** 1,2 ± 0,12** The spleen (mg) 1,0 ± 0,11 1,1 ± 0,1 1,3± 0,1** 1,4 ± 0,14** Lungs (mg) 1,2 ± 0,13 2,4 ± 0,22 2,7 ± 0,21** 2,1 ± 0,22** Kidneys (mg) 0,9 ± 0,075 1,4 ± 0,13 1,4 ± 0,11** 1,2 ± 0,11** The fat layer (mg) 2,4 ± 0,25 8,6 ± 0,84 7,9 ± 0,78** 3,4 ± 0,35** * - p<0.05 relative to the initial data; **- p<0.05 in relation to the control group Dynamics of body weight. The introduction of Brassica rapa polysaccharides at dose 25 mg/kg caused a significant (p<0.05) increase in body weight in animals of the control group who received only a diet, compared with the intact group. However, in the groups receiving Brassica rapa polysaccharides in various doses, there was a slowdown in the rate of body weight gain. This indicates a possible modulating effect of these biologically active substances on lipid metabolism and energy exchange in general. Obesity is a complex process involving the interaction of genetic, metabolic and environmental factors. Obesity, especially the accumulation of adipose tissue in the abdominal area (visceral obesity), is associated with impaired insulin function. Adipose tissue, especially visceral tissue, is an active endocrine organ that secretes various molecules, including cytokines, hormones, and free fatty acids. These substances can negatively affect the sensitivity of cells to insulin. In particular, free fatty acids (for example, palmitic acid) disrupt the normal functioning of insulin receptors, which leads to a decrease in the effectiveness of insulin. This, in turn, causes the need to increase its production by the pancreas, which over time can lead to its depletion. Secondly, the effect of inflammation. Obesity is accompanied by chronic low-level inflammation. Adipose tissue, especially visceral tissue, secretes various inflammatory mediators such as cytokines (e.g., interleukin-6 and TNF-α), which can disrupt insulin signaling. These inflammatory molecules affect the metabolism of carbohydrates, fats, and proteins, exacerbating insulin resistance. Chronic inflammation also contributes to the dysfunction of pancreatic beta cells, which reduces their ability to synthesize insulin. Thirdly, a violation of fat metabolism against the background of obesity increases the level of free fatty acids in the blood, which can lead to a violation of lipid metabolism. These acids have a toxic effect on pancreatic beta cells, disrupting their function and promoting apoptosis (programmed cell death).
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 60 This impairs the ability of the pancreas to produce insulin, which contributes to the development of hyperglycemia and diabetes mellitus. Fourth, ectopic fat accumulation, with the development of obesity, fat can be deposited not only in subcutaneous, but also in extravascular tissues (for example, in the liver, muscles and pancreas). Fat cells in these tissues contribute to the deterioration of insulin sensitivity, disrupting the normal metabolism of carbohydrates and fats. This can lead to abnormalities in glucose regulation and the development of diabetes. Fifth, decreased insulin secretion. Obesity can also affect the secretion of insulin by beta cells of the pancreas. Against the background of insulin resistance, beta cells begin to compensate for the body's increased need for insulin by increasing its production. However, over time, this compensatory increase may not be sufficient, and the pancreas may not be able to cope with the required level of insulin production. This leads to a decrease in insulin secretion and the development of hyperglycemia. Obesity is associated with changes in the composition of the microbiota, which can affect inflammatory processes, the metabolism of fatty acids and carbohydrates, as well as the functioning of the intestinal barrier. This, in turn, can contribute to the development of diabetes. Biochemical parameters of blood. Changes in the activity of AlT (alanine aminotransferase) and AsT (aspartate aminotransferase) enzymes in hyperlipidemia in a mouse model can serve as an indicator of liver damage associated with impaired lipid metabolism. AlT is more specific to the liver, reflecting hepatocellular damage, AsT is found not only in the liver, but also in the heart, muscles, and kidneys, so its increase may reflect a more systemic lesion. With hyperlipidemia, AlT and AsT levels increase in mice, which is often observed with induced hyperlipidemia (for example, a high-fat diet). This indicates fatty liver infiltration - steatosis. Damage to Table 3 In vivo activity under conditions of hyperlipidemia induсed in rats (М±m, n=40) Parametrs* Physiological Norm Control Metmоrfin 95 mg/kg BRP 20 mg/kg Total cholesterol mmol/l 1,7±0,05 2,9 ±0,25 1,9±0,18* 1,79 ±0,02* Triglycerides mmol/l 0,89±0,03 1,45 ±0,142 1,1±0,11 1,0 ±0,087* High-density lipoproteins, riglycerides, HDL mmol/l 0,84±0,082 0,44 ±0,041 0,89±0,086* 0,92±0,09* Low-density lipoproteins, LDL mmol/l 0,69±0,06 1,2 ±0,12 0,75±0,072* 0,88 ±0,078* Glucose 4,2 ±0,4 10,2±1,0 6,8±0,67* 6,2±0,6* AlT 58 ± 4,9 89,7± 8,9 71,5 ± 6,9 69,2 ± 6,8 AsT 46,8±3,8 69,8 ± 6,82 52,4 ± 5,1 54,3 ± 5,2 Total protein 69,0 ±6,0 48,1 ±4,6 56,8 ±5,8 65,8 ±5,4*
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 61 Glucosidase 1,95 ± 0,32 2,01 ± 0,31 1,98 ± 0,12 2,045 ± 0,26 Pancreatic amylase 2929,0 ± 38,7 2969,8 ± 39,8 2982,4 ± 39,2 2981,1 ± 40,2 Amylase of the small intestine 28,87 ±2,37 34,26 ± 3,4 34,10 ± 3,3 29,85 ± 2,9 *- p<0.05 in relation to the control group hepatocytes leads to the release of these enzymes into the bloodstream. AsT/AlT ratio: with liver steatosis, AlT>AsT is more common, which may indicate more pronounced damage, fibrosis, or additional muscle destruction. The association with inflammation and oxidative stress is expressed in the fact that hyperlipidemia causes oxidative stress, provoking inflammation in the liver. It can also increase AlT and AsT levels. Changes in AlT and AsT levels in hyperlipidemia in rats reflect the degree of liver damage and can be used as a biochemical marker of the toxicity of a high-fat diet. In animals with hyperlipidemia, there was an increase in total cholesterol (OH), triglycerides (TG), low-density lipoproteins (LDL) and a decrease in high-density lipoproteins (HDL). After the introduction of Brassica rapa polysaccharides for 4 weeks, there was a significant decrease in OH and TG levels, a restoration of the LDL/HDL ratio, and a decrease in serum glucose levels. These changes correlated with a slowdown in body weight gain, which suggests that a decrease in hyperlipidemia is directly related to the regulation of energy metabolism. Activity of digestive enzymes. Glucosidases (e.g. maltase, sucrase, isomaltase) break down disaccharides into monosaccharides (e.g. glucose), which are absorbed into the blood. Hyperlipidemia: The direct effect is not well understood, but microcirculation disorders and chronic inflammation can reduce the activity of glucosidases. 2. Alpha-amylase of the pancreas. Alpha-amylase breaks down starch into oligosaccharides. Hyperlipidemia: Can cause pancreatitis, which leads to a sharp increase in the level of amylase in the blood. Chronic inflammation or lipotoxicity can reduce the enzymatic activity of the pancreas over time. To assess the effect of polysaccharides on enzymatic activity, serum levels of pancreatic and small intestine amylase were measured. In animals treated with Brassica rapa polysaccharides, amylase activity was increased, which may be a compensatory reaction to excess fats and carbohydrates. After the introduction of polysaccharides, normalization of these parameters was observed: lipase activity decreased to values close to the intact group, amylase showed a tendency to stabilize, trypsin activity changed slightly, indicating a selective effect on carbohydrate-fat metabolism. Correlation analysis revealed significant correlations (p<0.05) between body weight dynamics and the following indicators: direct correlation between body weight and TG (r = 0.78) and OH (r = 0.72), positive correlation between amylase activity and glucose level (r = 0.69). Rapeseed polysaccharides and metmorphine contributed to the reduction of these indicators. The introduction of rapeseed polysaccharides contributed to the restoration of the activity of these enzymes, which indicates a positive effect on the digestive function. These data confirm the hypothesis that Brassica rapa polysaccharides are able to modulate metabolic processes, affecting both the blood lipid spectrum and the enzymatic activity of the digestive system, which, in turn, affects the body weight of animals. Studies of the interaction of Brassica rapa polysaccharides with animal body weight dynamics, blood biochemical parameters, and digestive enzyme activity in induced hyperlipidemia in rats show promising results.
SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 62 In particular, Brassica rapa polysaccharides demonstrated the ability to reduce the levels of total cholesterol (OH), triglycerides (TG) and low-density lipoproteins (LDL-C) in the blood serum of rats, as well as increase the level of high-density lipoproteins (HDL-C). Thus, Brassica rapa polysaccharides have an effect on the dynamics of animal body weight, blood biochemical parameters and the activity of digestive enzymes in induced hyperlipidemia in rats, which opens up prospects for their use as functional additives for the correction of lipid metabolism disorders. The results of this study confirm the hypothesis that rapeseed polysaccharides have a hypolipidemic effect. Weight loss and normalization of blood biochemical parameters may be associated with improved lipid metabolism and restoration of liver function. The effect on the activity of digestive enzymes may indicate an improvement in digestive function and nutrient absorption. Brassica rapa polysaccharides led to normalization of ALT and AST levels (approaching the control values), as well as increased activity of amylase and glucosidase to physiological values. The total protein level in the blood did not change significantly in the group of animals treated with Brassica rapa polysaccharides. Discussion Hyperlipidemia is an important risk factor for diabetes mellitus [11, 12, 13]. Hyperlipidemia is a condition characterized by abnormal levels of lipids in the blood, in particular, elevated levels of total cholesterol (OH), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), in addition to lowered levels of high-density lipoprotein cholesterol (HDLC). These changes are often accompanied by fatty liver and obesity [14]. From a biochemical point of view, a high-fat diet can cause an inflammatory reaction of the body [15] and increase the production of reactive oxygen species [16]. Currently, hyperlipidemia is mainly treated with diet or medication, among which statins are the most widely used lipid-lowering drugs; however, relapse is often observed after discontinuation of medication [17]. Patients with hyperlipidemia often use herbal products as an additional medicine. an alternative method or as an additional therapy [18]. Some common mechanisms of action of these herbs include inhibition of lipid biosynthesis by inhibiting HMG-CoA reductase [19, 20], as well as inhibition of other enzymes of cholesterol biosynthesis and lipolysis [21, 22]. Conclusion These herbs also control the level of lipids in the blood, regulating the process of lipid absorption, as well as the excretion of lipids and cholesterol from the body [23-24]. Many natural polysaccharides have been shown to have therapeutic effects on hyperlipidemia, although a comprehensive understanding of these properties has not yet been achieved. the effect remains unclear. The biological activity of polysaccharides depends on the molecular weight (MW), the composition of monosaccharides, the type of glycoside bonds, and the sulfate content [25]. The mechanism by which lipid reduction is achieved is complex because it affects multiple targets and cellular signaling pathways. One of the potential sources of biologically active polysaccharides, rapeseed polysaccharides effectively reduce glycemia and improve the lipid profile due to their antioxidant and anti-inflammatory properties. Studies have shown that turnips contain many active substances: glucosides, isothiocyanates [26, 27]. Induced hyperlipidemia is an experimental model widely used to evaluate the effectiveness of lipid-lowering drugs. The present study investigated the effect of polysaccharides on body weight, blood chemistry, and digestive enzyme activity in rats with hyperlipidemia caused by a high-fat diet. Plant polysaccharides, in particular polysaccharides isolated from turnip seeds, are able to regulate metabolism, have hypolipidemic and antiinflammatory effects.
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